The major project in the laboratory is to determine pathogenetic mechanisms involved in the development of paraffin oil (pristane) induced plasmacytomas in BALB/c mice. BALB/cAn mice are highly susceptible to developing these tumors while most other strains are resistant. Over 95% of plasmacytomas induced by pristane have chromosomal translocations [rcpt(12;15), rcpt(6;15)] involving directly or indirectly the c-myc locus on chr 15. The principle problems on which we are working are: 1) to identify the genes that determine susceptibility to plasmacytoma induction; 2) to identify additional critical oncogenic mutations that cooperate with c-myc using rapid plasmacytoma induction by infecting pristane-treated mice with transforming retroviruses that contain c-myc and a second cooperating oncogene; and 3) to determine the biological effects of pristane and how it acts in plasmacytoma induction. We have localized two genes that determine resistance to plasmacytoma induction and are concentrating on finding an exact location of one of the Pctr-1 on chr 4. We have found three oncogenes (v-abl, v-Ha-ras, and v-raf-1) that can cooperate with myc in transforming plasmacytomas and we are testing new viruses containing new combinations of oncogenes. Plasmacytomas originate in the mesenteries of the small intestine and appear to progress slowly by forming new satellite foci.